Article
Biochemistry & Molecular Biology
Erich Michel, Stefano Cucuzza, Peer R. E. Mittl, Oliver Zerbe, Andreas Plueckthun
Summary: The study aims to improve the stability of proteins for applications in therapeutics, diagnostics, and basic research. By designing a novel N-cap protein, the stability of proteins was successfully enhanced, addressing the issue of partial unfolding and making the proteins more resistant to proteolysis and aggregation.
Article
Biochemical Research Methods
Patrick C. Freitag, Fabian Brandl, Dominik Brucher, Fabian Weiss, Birgit Dreier, Andreas Pluckthun
Summary: Efficient and cell-specific DNA delivery is crucial for the safe and effective use of gene delivery technologies. The adapter technology described in this study redirects a commonly used human adenovirus to a specific cell population by blocking its natural tropism and allowing fusion with a retargeting module. By expanding the nature of the cell-binding portion, the modularity and applicability of this adapter technology is increased, allowing receptor-specific transduction mediated by different types of binding modules. This modular design enables efficient and specific mono- or dual-targeting without the need for tedious optimization procedures, making it valuable for gene therapy, synthetic biology, and biotechnology research.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Dentistry, Oral Surgery & Medicine
C. Huang, F. Sanaei, W. P. R. Verdurmen, F. Yang, W. Ji, X. F. Walboomers
Summary: The development of microfluidics-based microphysiological systems (MPSs) is leading to a shift from traditional static cell cultivation to dynamic tissue culture. Organs-on-a-chip (OoCs) can accurately replicate the mechanical and anatomical structures of the oral environment. This review discusses chip materials, fabrication methods, and the application of OoCs in in vitro culture, with a focus on dental, oral, and craniofacial (DOC) research. It also explores future perspectives such as model standardization and integrated platforms with advanced read-out functionality, highlighting the potential of OoCs as alternatives to animal testing and for developing predictive human models.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Jie Shi, Kristine Hauschulte, Ivan Mikicic, Srijana Maharjan, Valerie Arz, Tina Strauch, Jan B. Heidelberger, Jonas Schaefer, Birgit Dreier, Andreas Plueckthun, Petra Beli, Helle D. Ulrich, Hans-Peter Wollscheid
Summary: The study investigates the role of actin and associated molecules in the nucleus, focusing on the actin-based motor myosin VI in protecting stalled replication forks. The actin cytoskeleton is important for cellular structure and plasticity, but the abundance and function of filamentous actin in the nucleus are still debated.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Christoph Klenk, Maria Scrivens, Anina Niederer, Shuying Shi, Loretta Mueller, Elaine Gersz, Maurice Zauderer, Ernest S. Smith, Ralf Strohner, Andreas Pluckthun
Summary: The authors developed a method to alter the biophysical and functional properties of G protein-coupled receptors through directed evolution in mammalian cells. They evolved neurotensin receptor 1 for high stability and expression and demonstrated that receptors with complex molecular architectures and large ligands can also be evolved. Importantly, their approach allows for the evolution of functional receptor properties in the presence of the mammalian signaling environment, resulting in receptor variants with increased allosteric coupling.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Marine Blanc, Clara Lettl, Jeremy Guerin, Anais Vieille, Sven Furler, Sylvie Briand-Schumacher, Birgit Dreier, Celia Berge, Andreas Pluckthun, Sandrine Vadon-Le Goff, Remi Fronzes, Patricia Rousselle, Wolfgang Fischer, Laurent Terradot
Summary: The study focuses on Helicobacter pylori, a bacterial pathogen that injects the oncoprotein CagA into gastric cells using a type IV secretion system (cagT4SS). The research shows that CagI, a protein present on the surface of the bacterium, is crucial for the formation of the pilus that facilitates CagA delivery. DARPins targeting CagI are identified as potent inhibitors of the cagT4SS, which is a major risk factor for gastric cancer development.
Article
Biology
Rajib Schubert, Taegeun Bae, Branko Simic, Sheena N. Smith, Seong-Ho Park, Gabriela Nagy-Davidescu, Viviana Gradinaru, Andreas Pluckthun, Junho K. Hur
Summary: Tissue clearing combined with deep imaging is a powerful tool for expanding classical histological techniques. However, imaging highly melanin-rich tissues remains challenging. To address this, researchers developed a CRISPR-based gene editing method called CRISPR-Clear, which can be incorporated into existing tissue-clearing workflows. The method was successfully applied to melanoma tumors, allowing detailed characterization through staining and imaging techniques.
COMMUNICATIONS BIOLOGY
(2023)
Review
Oncology
M. Chernyavska, M. Masoudnia, T. Valerius, W. P. R. Verdurmen
Summary: Cancer immunotherapy is a promising approach in cancer treatment, but the translation from preclinical to clinical stages is a challenge. Microfluidic tumor models provide a bridge between in vitro and in vivo systems, enabling the study of complex tumor microenvironment and cancer-immune interactions. This review analyzes the applications of microfluidic models in cancer immunotherapy development, discusses their validation for predicting in vivo outcomes, and suggests next steps for implementation.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ruben D. Houvast, Nada Badr, Taryn March, Lysanne D. A. N. de Muynck, Vincent Q. Sier, Timo Schomann, Shadhvi Bhairosingh, Victor M. Baart, Judith A. H. M. Peeters, Gerard J. P. van Westen, Andreas Plueckthun, Jacobus Burggraaf, Peter J. K. Kuppen, Alexander L. Vahrmeijer, Cornelis F. M. Sier
Summary: This study evaluated the preclinical potential of EpCAM-binding DARPins for NIRF and PA imaging of cancer, demonstrating clear tumor delineation in vivo.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Biochemistry & Molecular Biology
Sarah Klinnert, Corinne D. Schenkel, Patrick C. Freitag, Huldrych F. Guenthard, Andreas Plueckthun, Karin J. Metzner
Summary: This study uses gene therapy to target and eliminate cells infected with HIV-1 by activating latent virus and killing the cells. This targeted gene therapy approach has the potential to effectively and safely eliminate infected cells.
Article
Oncology
Valentina Palacio-Castaneda, Bas van de Crommert, Elke Verploegen, Mike Overeem, Jenny van Oostrum, Wouter P. R. Verdurmen
Summary: Researchers have developed modular engineered proteins that can selectively degrade Ras in tumor cells that overexpress EpCAM, using endopeptidases fused with either Pseudomonas aeruginosa exotoxin A or diphtheria toxin. These proteins showed effective Ras degradation and selective toxicity towards tumor cells in both 2D and 3D tumor models, while non-cancerous fibroblasts remained unaffected.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Immunology
Liridona Maliqi, Nikolas Friedrich, Matthias Glogl, Stefan Schmutz, Daniel Schmidt, Peter Rusert, Merle Schanz, Maryam Zaheri, Chloe Pasin, Cyrille Niklaus, Caio Foulkes, Thomas Reinberg, Birgit Dreier, Irene Abela, David Peterhoff, Alexandra Hauser, Roger D. Kouyos, Huldrych F. Guenthard, Marit J. van Gils, Rogier W. Sanders, Ralf Wagner, Andreas Plueckthun, Alexandra Trkola
Summary: Understanding the balance between epitope shielding and accessibility on HIV-1 envelope trimers is crucial for selecting immunogens for bnAb-based vaccines. This study introduces a strategy using synthetic DARPin libraries to investigate the antigenic properties of Env immunogens. The in vitro screening tool, DANA, can provide relevant information of antigenic features of Env immunogens. The findings demonstrate that stronger trimer stabilization leads to the selection of highly mutated DARPins, mirroring observations made for bnAbs. By mimicking immunization regimens, DANA can be used to select immunogen combinations that favor trimer-reactive binders.
Article
Biochemistry & Molecular Biology
Melanie Gut, Birgit Dreier, Sven Furler, Jens Sobek, Andreas Pluckthun, Jason P. Holland
Summary: Late-stage prostate cancer often becomes resistant to standard chemotherapy and transforms into a hormone-resistant, drug-resistant, and incurable disease. Developing non-invasive tools to detect biochemical changes that indicate drug efficacy and identify drug resistance could have significant implications in managing individual patients' treatment plans. In this study, new Designed Ankyrin Repeat Proteins (DARPins) with high affinity for prostate-specific antigen (PSA) were selected using ribosome display and in vitro screening tools. These PSAbinding DARPins showed nanomolar affinity for PSA and could be radiolabeled for potential use in imaging-based monitoring of androgen receptor (AR)-targeted therapies.
RSC CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Baumann, Wan-Chin Chiang, Renato Valsecchi, Simon Jurt, Mattia Deluigi, Matthias Schuster, Karl Johan Rosengren, Andreas Pluckthun, Oliver Zerbe
Summary: This study investigates the rapid side-chain dynamics of an alpha(1B)-adrenergic receptor using methyl relaxation. The results show that the overall side-chain dynamics of the receptor are similar in the presence of different ligands. However, the allosteric ligand increases the flexibility of certain key residues, suggesting differences in the mechanisms for receptor activation. These findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.
Meeting Abstract
Biotechnology & Applied Microbiology
Sebastian Schellhorn, Dominik Bruecher, Natascha A. Wolff, Katrin Schroeer, Erwan Sallard, Kemal Mese, Wenli Zhang, Eric Ehrke-Schulz, Frank Thevenod, Andreas Plueckthun, Anja Ehrhardt